In recent years, genomic or other molecular tests have been recommended for clinical practice in the area of cancer treatment. They are used to identify individuals at high risk, screen and perform early detection, identify prognostic markers, and guide course of therapy. We propose a focused program of research that will investigate the comparative effectiveness of several tests related to colorectal cancer. The proposed study is a collaboration of several of the member sites of the NCI-funded Cancer Research Network (CRN) and academic partners. Our comprehensive research program in GPM for colorectal cancer will have two main components: 1) secondary data collection through evidence synthesis and cost-effectiveness analysis, and 2) primary data collection through a proof-of-principle study to examine questions about personalized medicine for colorectal cancer. In the proof-of-principle study, we will evaluate the utilization of KRAS and Lynch Syndrome genetic tests within our health systems, and measure the effectiveness of KRAS testing compared with a patient population that does not receive testing. We will also conduct patient and physician interviews to measure psychosocial issues related to KRAS testing, and to help us understand how the genetic test results are used to inform decisions. Our research program in colorectal cancer will build the experience, data systems, and methods that can apply to other cancer-related genetic or molecular tests in the future, such as UGT1A1 testing, or Oncotype DX and CYP2D6 testing for breast cancer. The interwoven research program that we propose will provide opportunities for synergy between teams of researchers conducting primary and secondary data collection. PUBLIC HEALTH RELEVANCE: We will study several genetic tests related to colon cancer that may help doctors understand who will get colon cancer and what therapies some patients should receive. We will study who gets tested, how the genetic test result helps people decide what to do, and whether patients have different health outcomes when they get tested. We will also summarize research that has already been published and analyze cost information about the use of these tests.